NM_006939.4:c.3490-4dupT
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_006939.4(SOS2):c.3490-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,172,574 control chromosomes in the GnomAD database, including 122,644 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_006939.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SOS2 | ENST00000216373.10 | c.3490-4_3490-3insT | splice_region_variant, intron_variant | Intron 22 of 22 | 1 | NM_006939.4 | ENSP00000216373.5 | |||
SOS2 | ENST00000543680.5 | c.3391-4_3391-3insT | splice_region_variant, intron_variant | Intron 21 of 21 | 1 | ENSP00000445328.1 |
Frequencies
GnomAD3 genomes AF: 0.588 AC: 83744AN: 142358Hom.: 24305 Cov.: 0
GnomAD3 exomes AF: 0.543 AC: 56372AN: 103896Hom.: 11623 AF XY: 0.543 AC XY: 30863AN XY: 56850
GnomAD4 exome AF: 0.520 AC: 535707AN: 1030130Hom.: 98341 Cov.: 24 AF XY: 0.520 AC XY: 259067AN XY: 497984
GnomAD4 genome AF: 0.588 AC: 83767AN: 142444Hom.: 24303 Cov.: 0 AF XY: 0.583 AC XY: 40143AN XY: 68842
ClinVar
Submissions by phenotype
not specified Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Variant summary: SOS2 c.3490-4dupT alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.55 in 131430 control chromosomes, suggesting that it is the major allele and therefore benign. A ClinVar submission (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign. -
Noonan syndrome 9 Benign:2
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Noonan syndrome and Noonan-related syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at